Bottom Line:
Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects.Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible.Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome.

Affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America. roger.kouyos@uzh.ch

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is an important cause of morbidity and mortality in both hospitals and the community. Traditionally, MRSA was mainly hospital-associated (HA-MRSA), but in the past decade community-associated strains (CA-MRSA) have spread widely. CA-MRSA strains seem to have significantly lower biological costs of resistance, and hence it has been speculated that they may replace HA-MRSA strains in the hospital. Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects. Here we assess the impact of competition between HA- and CA-MRSA using epidemiological models which integrate realistic data on drug-usage frequencies, resistance profiles, contact, and age structures. By explicitly accounting for the differing antibiotic usage frequencies in the hospital and the community, we find that coexistence between the strains is a possible outcome, as selection favors CA-MRSA in the community, because of its lower cost of resistance, while it favors HA-MRSA in the hospital, because of its broader resistance spectrum. Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible. Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome.

ppat-1003134-g008: Coexistence between MSSA, HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA/MSSA-infected host population in the treatment- and age-structured model.Colors (see legend) indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (MSSA/CA-MRSA).

Mentions:
When we consider the interaction between all three strains by including MSSA as one of the initial resident strains, we find that the parameter range in which all three strains can coexist shrinks successively with increasing time (see Figure 8) and eventually vanishes (results not shown). This is not unexpected, as the model structure assumes that the hospital and the community are two different ecological niches, which can thus maximally support the coexistence of only two strains over the long-term. However, we do find that all three strains can coexist for a broad range of conditions during a long transient time-span of several decades. Overall, these results indicate that transient effects can strongly extend the range of coexistence, and even allow for long-term de-facto coexistence where this would not be expected at equilibrium.

ppat-1003134-g008: Coexistence between MSSA, HA-MRSA and CA-MRSA in the transient phase after the introduction of CA-MRSA into the HA-MRSA/MSSA-infected host population in the treatment- and age-structured model.Colors (see legend) indicate which strains have frequencies >5% among the colonized patients in the hospital (HA-MRSA) and the community (MSSA/CA-MRSA).

Mentions:
When we consider the interaction between all three strains by including MSSA as one of the initial resident strains, we find that the parameter range in which all three strains can coexist shrinks successively with increasing time (see Figure 8) and eventually vanishes (results not shown). This is not unexpected, as the model structure assumes that the hospital and the community are two different ecological niches, which can thus maximally support the coexistence of only two strains over the long-term. However, we do find that all three strains can coexist for a broad range of conditions during a long transient time-span of several decades. Overall, these results indicate that transient effects can strongly extend the range of coexistence, and even allow for long-term de-facto coexistence where this would not be expected at equilibrium.

Bottom Line:
Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects.Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible.Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome.

Affiliation:
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America. roger.kouyos@uzh.ch

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) is an important cause of morbidity and mortality in both hospitals and the community. Traditionally, MRSA was mainly hospital-associated (HA-MRSA), but in the past decade community-associated strains (CA-MRSA) have spread widely. CA-MRSA strains seem to have significantly lower biological costs of resistance, and hence it has been speculated that they may replace HA-MRSA strains in the hospital. Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects. Here we assess the impact of competition between HA- and CA-MRSA using epidemiological models which integrate realistic data on drug-usage frequencies, resistance profiles, contact, and age structures. By explicitly accounting for the differing antibiotic usage frequencies in the hospital and the community, we find that coexistence between the strains is a possible outcome, as selection favors CA-MRSA in the community, because of its lower cost of resistance, while it favors HA-MRSA in the hospital, because of its broader resistance spectrum. Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible. Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome.